Quinolone is a kind of anti-infective drugs synthesized in recent years and clinically used for treating respiratory, gastrointestinal, urinary, dermatological, gynecological, surgical diseases and etc. extensively, with very good results. Prulifloxacin, the chemical name of which is (±)6-fluoro-1-methyl-7-[4-(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl-1-piperazinyl]-4-oxo-4H-[1,3]thiazeto[3,2-α]quinoline-3-carboxylic acid, is a quinolone drug developed together by Nippon Shinyaku Co. Ltd. and Meiji Seika Kaisha Ltd. Prulifloxacin is the third generation broad spectrum antibacterial drug of the fluoroquinolone class with broad spectrum antibacterial effects on both gram-positive bacteria and gram-negative bacteria and thereby can be used for treating systemic infection. In particular, antibacterial effects of prulifloxacin on Pseudomonas aeruginosa go beyond that of other commercially available antibacterial drugs of the fluoroquinolone class significantly. Results of clinical trials show that prulifloxacin have better therapeutic effects on dermatological infections, surgical infections, respiratory organ infections, urinary tract infections, biliary tract infections, infective enteritis, gynecological infections, ophthalmological infections, and otolaryngological infections.
Besides the common features of fluoroquinolone drugs, prulifloxacin have the following characteristics in comparison with other drugs of the same class: 1. its antibacterial effects on gram-positive bacteria are close to gatifloxacin but its effects on gram-negative bacteria such as Pseudomonas aeruginosa and etc. exceed similar products, for example, ciprofloxacin, ofloxacin, levofloxacin and gatifloxacin, and it also has effects on Pseudomonas aeruginosa of drug resistance. 2. It can be absorbed well via oral administration without accumulation in the body or distribution in cerebrospinal fluid and therefore has little side effect. 3. Its half-life is as long as 8-9 hours so that the times of taking medicines are less. 4. It takes effects fast and its peak blood concentration is attained within 0.5-1 hours. It has strong antibacterial activity. 5. It has hardly phototoxicity or neurotoxicity, so it is the safest product among fluoroquinolones at present.
Studies show that ulifloxacin has very strong antibacterial activity both in vivo and in vitro and has almost the same antibacterial spectrum as prulifloxacin: broad spectrum antibacterial effects on both gram-positive bacteria and gram-negative bacteria, strong antibacterial activity on Pseudomonas aeruginosa and other gram-negative bacteria particularly. Ulifloxacin has one carbon atom chiral center (1-C) resulting in two enantiomers of ulifloxacin. As reported in a publication (Chem. Pharm. Bull., 43(7), 1238-40 (English) 1995), the Japanese originator pharmaceutical company conducted pharmacodynamics studies on small samples obtained through chiral preparation chromatographic column and found that the antibacterial activity of levo-enantiomer is 2 to 8 times stronger than that of dextro-enantiomer.
After prulifloxacin is absorbed via oral administration, the side chain in 4′ site of piperazinyl is removed in the presence of hepatic enzyme, which results in that prulifloxacin is converted to ulifloxacin with the antibacterial activity and thereby taking action. The chiral center 1-C is not the metabolic site in this intracorporal process, so the metabolite of levo-prulifloxacin in the presence of hepatic enzyme is levo-ulifloxacin which has antibacterial effects. Predictably, the prospect for application of levo-prulifloxacin would be great. Although, there is one carbon atom chiral center (1-C) in the prulifloxacin structure, only racemic form (optical rotation [α]20D≈0°) can be obtained according to the prior arts. Thus, it is necessary to develop optically active prulifloxacin.